Rare Genetic Cases of Heterotopic Ossification

Abstract

Heterotopic Ossification (HO) is formation of normal bone in extraskeletal tissues, such as skin, subcutaneous tissue and deep connective tissue. Heterotopic ossification can be hereditary or nonhereditary in nature. We report two cases of rare hereditary forms of heterotopic ossification namely Fibrodysplasia Ossificans Progressiva (FOP) and Progressive Osseous Heteroplasia (POH). Hereditary forms of heterotopic ossification are progressive and severely debilitating in nature. Though these disorders are rare, awareness and knowledge about these disorders will help in early identification of such unique cases, leading to appropriate referral and management. Case Presentations Case 1A 4 year old Caucasian female was admitted with history of painful soft tissue swelling and induration on her right upper back, posterior neck and torso following an all-terrain vehicle accident that occurred a few weeks before her admission. Patient also reported trouble sitting up and increasing stiffness with ambulation. She had been evaluated in orthopedic clinic a few months previously for scoliosis and suspected Klippel-Feil anomaly. Physical examination revealed extensive tender indurated swellings over upper back and neck. She was also noted to have bilateral hallux valgus (Figure 1). Laboratory data revealed normal electrolytes, blood cell counts, liver enzymes, alkaline phosphatase and LDH levels. CT of her shoulder revealed a bony extension of the left anterior/inferior clavicle ( Figure 1) and was reported as exostosis of the clavicle with nonspecific soft tissue stranding through the lower neck and chest wall musculature, findings inconsistent with KlippelFeil syndrome. Genetic testing for FOP was done because of a strong clinical suspicion and due to the presence of hallux valgus, which revealed a c.617G>A transition in ACVR1 gene, resulting in a missense mutation (p.R206H), commonly associated with FOP [1]. Case 2A 17 year old Caucasian male presented to our endocrinology/bone clinic for evaluation of subcutaneous nodules. The lesions were first noted on his right index finger at two years of age. Over time similar lesions were noted on his right extremity. In the previous year he had noted more lesions in his right hand with extension into the forearm. He also had complaints of mild right wrist joint pain and stiffness with activity. He had undergone surgical removal of the lesions repeatedly (seven times). Family history was negative for ectopic ossifications, rickets, hormone deficiencies or other bone disorders. There was no history of consanguinity.Physical examination showed a well appearing Tanner V adolescent, with no features of Albright Hereditary Osteodystrophy (AHO). Extremity examination was remarkable for 2-4 mm sized bony lesions palpable in the inter-digital space of right index and middle finger and also extending along the radial aspect of the forearm. He was noted to have decreased mobility of the index and middle fingers. Similar lesions were noted on the dorsal aspect of the second digit ...

Heterotopic Ossification of Left Hip after Sport Injury; Imaging Techniques and Features in Early and Late Presentation

“…While hereditary HO develops in rare, progressive and life-threatening genetic diseases such as fibrodysplasia ossificans progressive, progressive osseous heteroplasia and Albright's hereditary osteodystrophy [8].…”